Autologous Hsp70 induces antigen specific Th1 immune responses in a murine T-cell lymphoma

Heat Shock protein-70 derived from tumor cells is highly immunogenic and induces specific anti-tumor immune response by directly activating cytotoxic CD8(+) T cells. Additionally, Hsp70 is known to be a strong activator of antigen presenting cells and therefore, up regulates the production of pro-inflammatory cytokines and chemokines. In this study, we have shown the effect of tumor-derived Hsp70 on the induction of delayed type hypersensitivity reaction in a T cell lymphoma bearing mice. The autologous Hsp70 augments contact hypersensitivity and delayed type hypersensitivity responses in mice challenged with allergen in vehicle and antigens respectively. The adoptive transfer of splenocytes derived from Hsp70 immunized mice is able to enhance delayed type hypersensitivity response in antigen challenged normal and DL-bearing host. Furthermore, adoptive transfer of macrophages incubated with autologous Hsp70 also enhances DTH reactivity in mice. The pro-inflammatory cytokines and C-C chemokines are found to be elevated in the DTH footpad extract of antigen challenged normal and DL-bearing mice. Increased production of IFN-gamma and MIP-1alpha+/- suggest that autologous Hsp70 augments the recruitment of antigen specific Th1 cells, which further secretes pro-inflammatory cytokines and C-C chemokines mediating the hypersensitivity reaction upon challenge with antigens.